The Pill

Having finally stopped taking the pill around 4 years ago, after experiencing 18 relatively periodless years, I can honestly say there has since been a moment every 21 days during which I seriously contemplate going back on it. 

I was fortunate enough not to suffer from any of the negative side-effects listed on the package insert, except perhaps a spot of melasma; though that did eventually fade away after I had stopped taking the pill.

How nice it was to know almost to the hour of the day when my period was coming; and then to have it last only a day or two. 

How nice it was not to feel like Freddie Krueger was shredding my uterus from the inside out. 

How nice it was to have had the option of taking the pill through my period when I was going on vacation so that I could enjoy my holiday without fear of the flood gates opening.

How nice it was not to be unpleasantly surprised by, 'nature's way of letting us know everything is functioning normally' at the most inopportune moments. 

Image from screenjunkies.com

(TOO MUCH? Sorry, too many years spent working in animal welfare has left me scarred with a rather dark, twisted and oft inappropriate sense of humour.)

Alas, I went off the pill for one of those long story kind of reasons that essentially translates into my having wanted to give my body a break; to allow it to cleanse; to be natural and chemical free. 

No doctor ever advised me to go off the pill; nor did any of the literature I read previously or since.

And yes, I do miss it. And perhaps the whole cleanse thing is not me being entirely honest because other factors figured into the decision as well; not the least of which was the fact that I moved (meaning I lost my GP) and was too lazy to go and find a new doctor to renew my prescription; that, combined with the feeling of dread at the thought of encountering yet another physician who responds to my request with the bedside manner of a Spanish Inquisitor.  

When I was a teenager and encountered such reluctance at the walk-in clinic, I would pitch my request as being the necessary means for me to regulate my periods. It wasn't a complete lie. The necessary means part was true, the regular periods part was just a welcome bonus. The thing is, going back twenty-some-odd years, (and maybe still today?) the fear of a teenage pregnancy by far outweighed the momentary discomfort of a disapproving physician. 

Then again, maybe at the time it was all just in my head, manifestations of a deep-seated sense of Catholic guilt. Or maybe it was the manifestation of a deep-seated sense of Catholic guilt that had prompted the physicians' scrutiny in the first place. Like how I always blurt-confess to customs officials at the airport about the pack of gum in my pocket or half-drunk bottle of whatever in my luggage.

Still, even when I was older there were times when I found myself faced with the same, though different, scrutinizing stare at the doctor's office. Different in the sense that with age the guilt was no longer stemming from my asking for a 'get out of jail free card' but rather from my curious lack of desire to procreate. 

I would suggest that this too was a manifestation of my own guilt if not for the fact that in many cases the doctors were rather overt in expressing their opinion on the matter; to such a degree that I often felt compelled to offer a verbal compromise: 

"I'm just not ready for kids yet ... but one day... (I promise?)" 

Anyway, enough of my self-analysis. Here are a few of the things I learned about the pill this week:

• Oral contraceptives are currently used by more than 100 million women worldwide. [28] 

•  Although the FDA approved the pill in 1960, it was not made available to unmarried women in all states until Eisenstadt v. Baird in 1972. [47] 

• Soon after it was legalized in the U.S., there was a sharp increase in graduation rates for women. [48]

• There are 2 main types of oral contraceptives: [1][26][27]

1. The combined oral contraceptive pill, which includes a combination of an estrogen (estradiol) and a progestogen (progestin).  
2. The mini-Pill which contains only progestin.

• Most synthetic progestins are chemical derivatives of testosterone. [1]

• If taken exactly as directed, birth control pills are 98% to 99% effective at preventing pregnancy. [8]

• Contraceptive efficacy may be impaired by: [27, 29-30]

• Missing more than one active pill in a packet. 

• Delay in starting the next packet of active pills.

• Intestinal malabsorption of active pills due to vomiting or diarrhea.

• Drug interactions with active pills that decrease contraceptive estrogen or progestin levels. 

According to Planned Parenthood, if you are late taking the mini-Pill by more than 3 hours, it’s important that you use a second form of birth control. This is because progestin, the active ingredient in the mini-Pill, typically stays in the body for only a short amount of time. [44]

MECHANISM OF ACTION, BRIEFLY

Menstrual Cycle

The follicular phase (days 1-14) is the phase of the menstrual cycle during which follicles in the ovary mature. It ends with ovulation. 

This phase is largely regulated by the hormone estradiol (a form of estrogen). [39]

The combined pill acts to inhibit follicular development and prevent ovulation. [36-38]

• Progestin acts to decrease gonadotropin releasing hormone.
• This decreases the secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH).
• Decreased FSH inhibits follicular development, preventing an increase in estradiol levels; which in turn prevents a mid-cycle luteinizing hormone surge, and ultimately ovulation.

• Additionally, all progestin-containing contraceptives inhibit sperm penetration through the cervix into the uterus and fallopian tubes by increasing the viscosity of the cervical mucus. [36] 

DRUG INTERACTIONS

The following medicines may reduce the effectiveness of oral contraceptives: [8][31-34][51] (List may not be comprehensive)

• Ampicillin
• Barbiturates
• Carbamazepine 
• Griseofulvin 
• Penicillin V
• Phenytoin 
• Primidone 
• Rifampin 
• Ritonavir 
• Tetracyclines 
• Troglitazone 

SIDE EFFECTS & ONGOING RESEARCH



MELASMA [49][50]

Melasma (patches of dark skin discoloration; often on the face) occurs in 10-25% of women taking oral contraceptives. The darkened pigmentation is due to overproduction of melanin.

WEIGHT GAIN

A 2011 review found that studies of combination hormonal contraceptives showed no large difference in weight gain when compared with placebo groups. [35]

The estrogen in birth control pills does affect fat (adipose) cells, making them larger but not more numerous. [8]

MEMORY

Results from a University of California study suggest that hormonal contraception alters memory of an emotional event. [2][3]

Two groups of healthy female subjects—one naturally cycling, one using hormonal contraception—viewed either a brief, emotionally arousing story, or a closely matched, but more emotionally neutral story.

When tested for memory recall a week later, naturally cycling women exhibited enhanced memory of story details, but not of central information (gist), in the emotional compared with neutral story conditions. In contrast, women using hormonal contraception exhibited enhanced memory of the gist of the story, but not the details, in the emotional compared with neutral story conditions. 

CROHN’S DISEASE

A study led by Harvard University gastroenterologist Dr. Hamed Khalili, compared the gastrointestinal health of 230,000 American women who used the pill for long periods of time with women who never used birth control pills. The study found there was an increased risk in women with a genetic predisposition to Crohn’s who had taken oral contraceptives for more than five years. [45][46]

VENOUS THROMBOEMBOLISM (BLOOD CLOTS)

Combined oral contraceptives increase the risk of venous thromboembolism (including deep vein thrombosis and pulmonary embolism), [42] ischemic stroke, [40] and cardiovascular disease among those at high risk. [41] These risks are compounded by smoking, especially in women over 35. [43] 

GLAUCOMA[4]

Researchers analysed data collected from a CDC survey of 3400 women aged 40 and older and found that women who had taken the pill for longer than 3 years were twice as likely to report having been diagnosed with glaucoma.

• Although this  study did not prove a direct causal relationship between taking oral contraceptives and the development of glaucoma, Dr. Shan Lin, lead researcher and professor of clinical ophthalmology at the University of California, San Francisco believes the correlation is strong enough to support further research. 

THE BRAIN 

• In this 2015 study [5][6] on the effects of androgenic and anti-androgenic progestins on fusiform and frontal gray matter volume and facial recognition, researchers found that: 

• Androgenic and anti-androgenic oral contraceptives differentially modulate human brain structure.

• Users of oral hormone contraceptives containing anti-androgenic progestins showed enhanced face recognition performance.

(To put a face to the jargon, some examples of products containing anti-androgenic progestins include: Diane™-35, Estelle™ 35 and Ginet-84™, Yasmin™, Yaz™, Valette™ [52]) 

• Gray matter volumes increased with duration of oral hormonal contraceptive use.

• Gray matter volumes in the hippocampus relate to duration of previous oral contraceptive use.

Left Cerebral Hemisphere

• In this 2015 study comparing the cortical thickness in the brains of oral contraceptive users and naturally cycling women, researchers at UCLA found that: [7]

• Oral contraceptive pill use was associated with significantly lower cortical thickness in the regions of the brain believed to be important for responding to rewards and evaluating internal states/incoming stimuli.

• Though whether oral contraception use is causally or only indirectly related to these changes in brain morphology remains to be determined. 

Dark violet outer layer is the cerebral cortex

ENDOMETRIAL CANCER

• Women who use oral contraceptives have been shown to have a reduced risk of endometrial cancer. This protective effect increases with the length of time oral contraceptives are used and continues for many years after a woman stops using oral contraceptives. [11][18]

CERVICAL CANCER

• Long-term use of oral contraceptives (5 or more years) is associated with an increased risk of cervical cancer. [11][19]

• An analysis of 24 epidemiologic studies found that the longer a woman used oral contraceptives, the higher her risk of cervical cancer. However, among women who stopped taking oral contraceptives, the risk tended to decline over time, regardless of how long they had used oral contraceptives before stopping. [11][20]

• In a 2002 report by the International Agency for Research on Cancer, which is part of the World Health Organization, data from eight studies were combined to assess the association between oral contraceptive use and cervical cancer risk among women infected with the human papillomavirus (HPV). Researchers found a nearly threefold increase in risk among women who had used oral contraceptives for 5 to 9 years compared with women who had never used oral contraceptives. Among women who had used oral contraceptives for 10 years or longer, the risk of cervical cancer was four times higher. [11][21]

• Virtually all cervical cancers are caused by persistent infection with high-risk, or oncogenic, types of HPV, and the association of cervical cancer with oral contraceptive use is likely to be indirect. The hormones in oral contraceptives may change the susceptibility of cervical cells to HPV infection, affect their ability to clear the infection, or make it easier for HPV infection to cause changes that progress to cervical cancer. [11]

• On the subject of HPV and cervical cancer, it perhaps bears reminding here that oral contraception is a form of birth control alone and does not confer protection against STD's. In short, get vaccinated, use condoms, get tested and be mindful of the risks involved in unprotected sex.

LIVER CANCER

• Oral contraceptive use is associated with an increase in the risk of benign liver tumors, such as hepatocellular adenomas. [11][22]  Benign tumors can form as lumps in different areas of the liver, and they have a high risk of bleeding or rupturing. However, these tumors rarely become malignant. [11][23]

• Whether oral contraceptive use increases the risk of malignant liver tumors (hepatocellular carcinomas), is less clear. Some studies have found that women who take oral contraceptives for more than 5 years have an increased risk of hepatocellular carcinoma, but others have not. [11]

BREAST CANCER

• The effect of birth control pills on breast cancer risk isn't clear. Some research indicates that birth control pills slightly increase the risk of breast cancer — but that 10 or more years after stopping the pill, a woman's breast cancer risk returns to the same level as if she had never taken birth control pills. [9][10] 

• A 2010 analysis of data from the Nurses’ Health Study, which has been following more than 116,000 female nurses who were 24 to 43 years old when they enrolled in the study in 1989, [12] found that the participants who used oral contraceptives had a slight increase in breast cancer risk. However, nearly all of the increased risk was seen among women who took a specific type of oral contraceptive, a “triphasic” pill, in which the dose of hormones is changed in three stages over the course of a woman’s monthly cycle. [11][12]

OVARIAN CANCER

• A 2002 analysis of data from the Cancer and Steroid Hormone study indicated that oral contraceptive formulations with high levels of progestin were associated with a lower risk of ovarian cancer than formulations with low progestin levels. [11][13]

• In the 2005 Steroid Hormones and Reproductions (SHARE) Study, researchers investigated new, lower-dose progestins that have varying androgenic (testosterone-like) effects. They found no difference in ovarian cancer risk between androgenic and non-androgenic pills. [11][14]

• Oral contraceptive use by women at increased risk of ovarian cancer due to a genetic mutation in the BRCA1 or BRCA2 gene has been the focus of much research. 

• One study showed a reduction in risk among BRCA1- or BRCA2-mutation carriers who took oral contraceptives, whereas another study showed no effect. [11][15-16] 

• And still another study, published in 2009, found that women with BRCA1 mutations who took oral contraceptives had about half the risk of ovarian cancer as those who did not. [11][17]

A PILL FOR THE FELLAS

• At least 4 types of hormonal male contraception are currently being tested: [53]

• Testosterone 

• Androgen/progestin combination

• Testosterone/gonadotropin releasing hormone combination

• Selective androgen and progestin receptor modulators. 

• All 4 methods of hormonal birth control try to stop or slow sperm production by interfering with some step in the sperm growth cycle. This creates a low sperm count, which could be reversed when the male stops using the contraceptive. [53]

• Ongoing research is testing the effectiveness, evaluating the safety and monitoring the side effects of the hormonal combination drug (testosterone & progestin) in 1,000 men in China. [53]

• Research published in 2013 found that blocking certain proteins in the bodies of male mice rendered them infertile, but did not affect their sexual behaviour or the quality of their sperm. It prevented the sperm cells from being launched during ejaculation. When the mice's sperm was used to artificially inseminate female mice, it resulted in pregnancies and healthy baby mice. [54][55]

Updates / Related

Women over 18 can now purchase birth control over-the-counter in Oregon / livehuffingtonpost.com/ January 11, 2016

Male Birth Control, Like Vasalgel, Is Closer To Becoming A Reality; Here's Everything We Know So Far / Medical Daily / July 15, 2015
UVA Discovers A Protein Essential To Fertilization, Bringing Us One Step Closer To Male Birth Control / Medical Daily / June 25, 2015

The Effectiveness Of Birth Control, Plus 3 More Things We Recently Learned About Birth Control Methods / Medical Daily / May 1, 2015

***

FIN

REFERENCES

[1] http://contraception.about.com/od/thepill/p/Progestins.htm

[2] http://www.sciencedaily.com/releases/2011/09/110909141637.htm

University of California - Irvine. "Birth control pills affect memory, researchers find." ScienceDaily. ScienceDaily, 9 September 2011. <www.sciencedaily.com/releases/2011/09/110909141637.htm>.

[3] Shawn E. Nielsen, Nicole Ertman, Yasmeen S. Lakhani, Larry Cahill. Hormonal contraception usage is associated with altered memory for an emotional story. Neurobiology of Learning and Memory, 2011; 96 (2): 378 DOI:10.1016/j.nlm.2011.06.013

[4] http://www.natureworldnews.com/articles/4968/20131119/birth-control-pills-may-increase-a-womans-risk-of-glaucoma.htm

[5] http://www.iflscience.com/health-and-medicine/oral-contraceptive-pill-associated-changes-brain-structure

[6] http://www.sciencedirect.com/science/article/pii/S0006899314016096

[7] http://onlinelibrary.wiley.com/doi/10.1002/hbm.22797/full

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[9] http://www.mayoclinic.org/healthy-lifestyle/birth-control/expert-answers/birth-control-pills/faq-20058110

[10] Contraceptives and cancer risk. National Cancer Institute. http://www.cancer.gov/cancertopics/factsheet/Risk/oral-contraceptives. (2, page 2)

[11]http://www.cancer.gov/cancertopics/causes-prevention/risk/hormones/oral-contraceptives-fact-sheet

[12] Hunter DJ, Colditz GA, Hankinson SE, et al. Oral contraceptive use and breast cancer: a prospective study of young women. Cancer Epidemiology Biomarkers and Prevention 2010; 19(10):2496–2502.

 [PubMed Abstract]

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[15] Narod SA, Risch H, Moslehi R, et al. Oral contraceptives and the risk of hereditary ovarian cancer. Hereditary Ovarian Cancer Clinical Study Group. New England Journal of Medicine1998; 339(7):424–428. [PubMed Abstract]

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[21] Moreno V, Bosch FX, Munoz N, et al. Effect of oral contraceptives on risk of cervical cancer in women with human papillomavirus infection: the IARC multicentric case-control study. Lancet2002; 359(9312):1085–1092. [PubMed Abstract]

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[28] Mosher WD, Martinez GM, Chandra A, Abma JC, Willson SJ (2004). "Use of contraception and use of family planning services in the United States: 1982–2002" (PDF). Adv Data (350): 1–36. PMID 15633582. all US women aged 15–44

[29] Organon (November 2001). "Mercilon SPC (Summary of Product Characteristics".

[30] Speroff, Leon; Darney, Philip D. (2005). "Oral Contraception". A Clinical Guide for Contraception (4th ed.). Philadelphia: Lippincott Williams & Wilkins. pp. 21–138. ISBN 0-7817-6488-2.

[31] The effects of broad-spectrum antibiotics on Combined contraceptive pills is not found on systematic interaction metanalysis (Archer, 2002), although "individual patients do show large decreases in the plasma concentrations of ethinylestradiol when they take certain other antibiotics" (Dickinson, 2001). "...experts on this topic still recommend informing oral contraceptive users of the potential for a rare interaction" (DeRossi, 2002) and this remains current (2006) UK Family Planning Association advice.

[32]  Archer JS, Archer DF (2002). "Oral contraceptive efficacy and antibiotic interaction: a myth debunked". J Am Acad Dermatol 46 (6): 917–23.doi:10.1067/mjd.2002.120448. PMID 12063491.

[33]  Dickinson BD, Altman RD, Nielsen NH, Sterling ML (2001). "Drug interactions between oral contraceptives and antibiotics". Obstet Gynecol 98 (5 Pt 1): 853–60. doi:10.1016/S0029-7844(01)01532-0. PMID 11704183.

[34] DeRossi SS, Hersh EV (2002). "Antibiotics and oral contraceptives". Dent Clin North Am 46 (4): 653–64. doi:10.1016/S0011-8532(02)00017-4.PMID 12436822.

[35] Gallo MF, Lopez LM, Grimes DA, Carayon F, Schulz KF, Helmerhorst FM (2014). "Combination contraceptives: effects on weight".Cochrane Database Syst Rev 1: CD003987. doi:10.1002/14651858.CD003987.pub5. PMID 24477630.

[36] Nelson, Anita L.; Cwiak, Carrie (2011). "Combined oral contraceptives (COCs)". In Hatcher, Robert A.; Trussell, James; Nelson, Anita L.; Cates, Willard Jr.; Kowal, Deborah; Policar, Michael S. (eds.). Contraceptive technology (20th revised ed.). New York: Ardent Media. pp. 249–341.ISBN 978-1-59708-004-0. ISSN 0091-9721. OCLC 781956734. pp. 257–258:

Mechanism of action
COCs prevent fertilization and, therefore, qualify as contraceptives. There is no significant evidence that they work after fertilization. The progestins in all COCs provide most of the contraceptive effect by suppressing ovulation and thickening cervical mucus, although the estrogens also make a small contribution to ovulation suppression. Cycle control is enhanced by the estrogen.
Because COCs so effectively suppress ovulation and block ascent of sperm into the upper genital tract, the potential impact on endometrial receptivity to implantation is almost academic. When the two primary mechanisms fail, the fact that pregnancy occurs despite the endometrial changes demonstrates that those endometrial changes do not significantly contribute to the pill's mechanism of action.

[37] Speroff, Leon; Darney, Philip D. (2011). "Oral contraception". A clinical guide for contraception (5th ed.). Philadelphia: Lippincott Williams & Wilkins. pp. 19–152. ISBN 978-1-60831-610-6.

[38] Levin, Ellis R.; Hammes, Stephen R. (2011). "Estrogens and progestins". In Brunton; Chabner, Bruce A.; Knollmann, Björn C. Goodman & Gilman's pharmacological basis of therapeutics (12th ed.). New York: McGraw-Hill Medical. pp. 1163–1194. ISBN 978-0-07-162442-8.

[39] Bagnell, C (2005). "Animal Reproduction". Rutgers University Department of Animal Sciences.

[40] Kemmeren JM, Tanis BC, van den Bosch MA, Bollen EL, Helmerhorst FM, van der Graaf Y, Rosendaal FR, Algra A (2002). "Risk of Arterial Thrombosis in Relation to Oral Contraceptives (RATIO) Study: Oral Contraceptives and the Risk of Ischemic Stroke". Stroke 33 (5): 1202–8.doi:10.1161/01.STR.0000015345.61324.3F. PMID 11988591.

[41] Baillargeon JP, McClish DK, Essah PA, Nestler JE (2005). "Association between the Current Use of Low-Dose Oral Contraceptives and Cardiovascular Arterial Disease: A Meta-Analysis". Journal of Clinical Endocrinology & Metabolism 90 (7): 3863–70. doi:10.1210/jc.2004-1958.PMID 15814774.

[42] Blanco-Molina A, Monreal M (2010). "Venous thromboembolism in women taking hormonal contraceptives". Expert Review of Cardiovascular Therapy 8 (2): 211–5. doi:10.1586/erc.09.175. PMID 20136607.

[43] Rang, Humphrey P.; Dale, Maureen M.; Ritter, James M.; Flower, Rod J.; Henderson, Graeme (2012). "The reproductive system". Rang and Dale's pharmacology (7th ed.). Edinburgh: Elsevier/Churchill Livingstone. p. 426. ISBN 978-0-7020-3471-8.

[44] http://www.medicaldaily.com/birth-control-women-why-you-should-take-pill-same-time-every-day-325660

[45] http://www.medicaldaily.com/birth-control-pill-may-triple-risk-crohns-disease-women-family-history-condition-325850

[46] Medical Daily Source: Khalili H, Higuchi LM, Ananthakrishnan AN, et al. Oral contraceptives, reproductive factors and risk of inflammatory bowel disease. Gut. 2012.

[47] Tone, Andrea (2001). Devices & Desires: A History of Contraceptives in America. New York: Hill and Wang. ISBN 0-8090-3817-X.

[48] Goldin, Claudia, and Lawrence Katz (2002). "The Power of the Pill: Oral Contraceptives and Women's Career and Marriage Decisions". Journal of Political Economy 110 (4): 730–770. doi:10.1086/340778.

[49] http://dermnetnz.org/colour/melasma.html

[50] http://www.dermalinstitute.com/us/library/118_article_Melasma_Unmasked.html

[51] http://www.mayoclinic.org/drugs-supplements/estrogen-and-progestin-oral-contraceptives-oral-route/precautions/drg-20069422

[52] Anti-androgen therapy. - DermNet NZ     www.dermnetnz.org/treatments/antiandrogens.html

[53] http://www.pamf.org/teen/sex/birthcontrol/malecontraceptive.html

[54] http://www.nhs.uk/Conditions/contraception-guide/Pages/male-pill.aspx

[55] http://www.nhs.uk/news/2013/12December/Pages/Early-research-on-male-pill-shows-promise.aspx

ADDITIONAL RESOURCES

http://en.wikipedia.org/wiki/Follicular_phase

http://www.breastcancer.org/research-news/study-questions-birth-control-and-risk

http://www.cancerresearchuk.org/about-cancer/cancers-in-general/cancer-questions/the-contraceptive-pill-and-cancer-risk

IMAGE CREDITS

"Opened Oral Birth Control" by Bryancalabro - Own work. Licensed under CC BY-SA 3.0 via Wikimedia Commons - http://commons.wikimedia.org/wiki/File:Opened_Oral_Birth_Control.jpg#/media/File:Opened_Oral_Birth_Control.jpg

"MenstrualCycle2 en" by Isometrik - Own work. Licensed under CC BY-SA 3.0 via Wikimedia Commons - http://commons.wikimedia.org/wiki/File:MenstrualCycle2_en.svg#/media/File:MenstrualCycle2_en.svg

"Gray727 parahippocampal gyrus" by Gray, vectorized by Mysid, colourd by was_a_bee. - File:Gray727.svg. Licensed under Public Domain via Wikimedia Commons - http://commons.wikimedia.org/wiki/File:Gray727_parahippocampal_gyrus.png#/media/File:Gray727_parahippocampal_gyrus.png

"Brainmaps-macaque-hippocampus" by brainmaps.org. Licensed under CC BY 3.0 via Wikimedia Commons - http://commons.wikimedia.org/wiki/File:Brainmaps-macaque-hippocampus.jpg#/media/File:Brainmaps-macaque-hippocampus.jpg

"VictorianPostcard" by Artist not credited - Argument in an Off Key.. Licensed under Public Domain via Wikimedia Commons - http://commons.wikimedia.org/wiki/File:VictorianPostcard.jpg#/media/File:VictorianPostcard.jpg